Accelerated T-cell senescence and persistent inflammation in older adults with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory condition primarily affecting the peripheral joints while also causing extra-articular complications. Adults with RA show premature aging of the immune system (immunosenescence). Here, we investigated whether senescence T-cell markers and inflammaging remain elevated in older adults with RA. Forty-four older adults were recruited, including 23 patients with RA and 21 age-matched controls. Plasma cytokines were determined by cytometric bead assays (CBAs). Peripheral blood mononuclear cells (PBMCs) were isolated and immunophenotyped using multicolor flow cytometry to identify different stages of T-cell differentiation (early, intermediate, and late) as well as senescent T cells (characterized by CD57, NKG2A, and NKG2D expression). PBMCs were also stimulated with lipopolysaccharide (LPS) to measure cytokine production in vitro (TNF-α, IL-1β, IL-6, IL-8, and IL-10) by CBAs. Older adults with RA patients exhibit elevated plasma levels of pro-inflammatory cytokines compared to controls. However, PBMCs of patients and controls secreted similar levels of cytokines. Older adults with RA had reduced proportions of early-differentiated T cells (CD27⁺CD28⁺) and an expansion of late-differentiated CD27^nullCD28^null (senescent) T cells compared to controls. T cells expressing markers of senescence (CD57, NKG2D, or NKG2A) were also found to be expanded compared to the control group. Finally, senescence-associated features were observed in patients with late-onset RA. Older adults with RA showed several features of immunosenescence and inflammaging, which could be involved in disease progression. These findings underscore the significance of immunosenescence in RA.